Our goal is to generate new information about the structure and function of blood vessels during the evolution of hypertension and after this disease is established. Changes in vascular function and structure will be analyzed as to the subcellular abnormalities responsible for the gross alteration. In addition to characterizing the differences between normotensive and hypertensive vessels, we will study abnormalities in extravascular physiology which may cause these vascular changes. This will be accomplished by obtaining data bearing on the sequence of events beginning with the experimental interventions that initiate the process and extending to the actual change in the vessel. Data will be obtained to determine whether the vascular change is secondary to the increase in wall stress or primary, and therefore possibly initiating the increase in total peripheral resistance of this disease. Two of the eight projects deal with both human and experimental studies, the remainder deal exclusively with animals. In six of the eight studies, the pig is used as the experimental animal. The eight projects are supported by five core facilities: Administration, Hypertensive Pig colony, Laboratory, Anatomy, and Biostatistics.